Lu AF28996 in Participants With Parkinson's Disease (PD)

Interventional, Open-label, Exploratory Study, Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Lu AF28996 in Patients With Parkinson's Disease

The purpose of this study is to investigate the safety of Lu AF28996, how well it is tolerated and what the body does to the drug in participants with Parkinson's disease.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Lu AF28996

Detailed Description

The study consists of different parts. Part A of the study will consist of once daily (OD) cohorts (OD Cohort 1 to 4[5]), as well as twice daily (BID) cohorts (BID Cohorts A1 and A2). Part B and Part C have been added to the study. Part B will consist of 2 cohorts (Cohorts B1 and B2) whereby participants will be administered Lu AF28996 BID. Part C will consist of 2 cohorts (Cohorts C1 and C2) whereby participants will be administered three times daily (TID) Lu AF28996.

• Study Type: Interventional
• Enrollment (Estimated): 77
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Email contact via H. Lundbeck A/S; Phone Number: +45 36301311; Email: LundbeckClinicalTrials@Lundbeck.com

Study Locations

• Netherlands
  • Leeuwarden, Netherlands, 8934 AD
    • Completed
    • QPS Netherlands BV
• United States
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Recruiting
      • Velocity
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Completed
      • Atlanta Center for Medical Research
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Quest Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Part A

• Participants diagnosed with idiopathic PD (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), with not more than 1 first-degree relative who has PD.
• Participants must have a Modified Hoehn and Yahr score ≤4 in the OFF state and ≤3 in the ON state, and a Mini Mental State Examination score >25.
• The OFF/ON amplitude on the MDS-UPDRS Part III at screening must be minimum 30% difference.
• Participants must experience recognizable and predictable motor fluctuations (with at least 1.5 hours of OFF periods in the awake time, including predictable morning OFF episodes), causing clinically significant disability during the 7-week Screening Period, as evaluated by the investigator. This will be documented using a participant ON/OFF state registration over 3 consecutive days prior to enrolment.
• Allowed concomitant medication for PD during the study includes levodopa, monoamine oxidase B inhibitors, COMT inhibitors, anticholinergics, and amantadine. Dopamine agonists are not allowed and should be discontinued ≥4 weeks prior to dosing with Lu AF28996 and until the end of the study.

Part B and Part C

• Participants diagnosed with idiopathic PD (consistent with the UK PD Society Brain Bank Criteria for the Diagnosis of PD), with not more than 1 first-degree relative who has PD.
• Participants must have a Modified Hoehn and Yahr score ≥2 to ≤4 in the OFF state and ≤3 in the ON state, a MDS-UPDRS Part IV, 4.5 score of 1 or 2, and a MDS-UPDRS Part IV, 4.2 score ≥2 (at least mild functional impact), and a Mini Mental State Examination score >25 at the Screening Visit.
• Participants must currently have a good response to levodopa and be receiving a stable dose of levodopa (≥3 doses per day of levodopa/dopa decarboxylase inhibitor therapy or ≥3 doses per day of levodopa Extended-Release Capsules and LEDD between 400 and 1600, inclusive) for at least 4 weeks prior to screening.
• Participants must experience recognizable and predictable motor fluctuations (with ≥3 hours of OFF periods in the awake time, including predictable morning OFF episodes), causing clinically significant disability during 3 months prior to enrolment, as evaluated by the investigator. The criteria will be documented using Hauser Diary over 3 consecutive days prior to enrolment.
• Participants must experience ≥1 hour daily ON time with troublesome dyskinesia (TD) in the awake time (TD/24 hours while awake) during the last 3 months prior to enrolment as evaluated by the investigator. The criteria will be documented using the Hauser Diary over 3 consecutive days prior to enrolment.
• Allowed concomitant medication for PD during the study includes levodopa, dopamine agonists, if allowed daily dose, monoamine oxidase B inhibitors, COMT inhibitors, anticholinergics, and amantadine.

Exclusion Criteria:

• The participant has or had one or more of the following conditions that are considered clinically relevant in the context of the study; other neurological disorder, psychiatric disorder, seizure disorder or encephalopathy, respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrinological disorder, haematological disorder, infectious disorder, any clinically significant immunological condition, or a history of narrow-angle glaucoma.
• Participant has been treated with apomorphine (pen/pump), or levodopa/carbidopa intestinal gel (LCIG), within 6 weeks prior to the Baseline Visit.
• Participants formerly treated with oral or transdermal dopamine agonists must have discontinued 4 weeks prior to screening.
• Participant has a history of Dopamine Agonist Withdrawal Syndrome (DAWS) when dopamine agonists were previously discontinued or reduced.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lu AF28996; Participants will receive ascending oral doses of Lu AF28996 OD for 14 days (Day 1 to Day 14) in all OD Cohorts 1-4 (5). On Day 15, the participant will initiate down-titration of Lu AF28996 as per Investigator's judgement. For the BID Cohort A1, participants will receive Lu AF28996 BID for 24 days (Day 1 to Day 24), followed by down-titration as per Investigator's judgement. For the BID Cohort A2, participants will receive Lu AF28996 BID for 39 days (Day 1 to Day 39), followed by down-titration as per Investigator's judgement. For Part B BID Cohorts B1 and B2, participants will receive Lu AF28996 BID for up to 49 days, followed by down-titration as per Investigator's judgement. For Part C TID Cohorts C1 and C2, participants will receive Lu AF28996 for up to 49 days, followed by down-titration as per Investigator's judgement.

Drug: Lu AF28996; capsule, orally, doses and dose escalation scheme will be decided upon at dosing conferences

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-emergent Adverse Events	Safety and tolerability based on the safety assessments (clinical safety laboratory tests, vital signs, weight, ECG parameters and physical examination)	From Baseline to Day 62
Amount of Lu AF28996, Lu AF28995, Lu AF29308, and Lu AF29309 Excreted in Urine		0 (predose) to 24 hours postdose on Day 1 to Day 62
AUC(last) of Lu AF28996	Area under the plasma concentration time curve from zero to last quantifiable plasma concentration	0 (predose) to 24 hours postdose on Day 1 to Day 41
AUC(0-24h) of Lu AF28996	Area under the plasma concentration time curve from zero to 24 hours post dose	0 (predose) to 24 hours postdose on Day 1 to Day 41
Cmax of Lu AF28996	Maximum observed plasma concentration of Lu AF28996	0 (predose) to 24 hours postdose on Day 1 to Day 41
CL/F of Lu AF28996	Oral clearance for Lu AF28996 in plasma	0 (predose) to 24 hours postdose on Day 1 to Day 41

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S
• Investigators: Study Director: Email contact via H. Lundbeck A/S, LundbeckClinicalTrials@Lundbeck.com

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2020
• Primary Completion (Estimated): July 20, 2025
• Study Completion (Estimated): July 20, 2025

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: February 28, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 18252A; 2019-001280-77 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No